Control of membrane sealing in injured mammalian spinal cord axons

Citation
Ry. Shi et al., Control of membrane sealing in injured mammalian spinal cord axons, J NEUROPHYS, 84(4), 2000, pp. 1763-1769
Citations number
20
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROPHYSIOLOGY
ISSN journal
00223077 → ACNP
Volume
84
Issue
4
Year of publication
2000
Pages
1763 - 1769
Database
ISI
SICI code
0022-3077(200010)84:4<1763:COMSII>2.0.ZU;2-N
Abstract
The process of sealing of damaged axons was examined in isolated strips of white matter from guinea pig spinal cord by recording the "compound membran e potential," using a sucrose-gap technique, and by examining uptake of hor seradish peroxidase (HRP). Following axonal transection, exponential recove ry of membrane potential occurred with a time constant of 20 +/- 5 min, at 37 degrees C, and extracellular calcium activity ([Ca2+](o)) of 2 mM. Most axons excluded HRP by 30 min following transection. The rate of sealing was reduced by lowering calcium and was effectively blocked at [Ca2+](o) less than or equal to 0.5 mM, under which condition most axons continued to take up HRP for more than 1 h. Sealing at higher [Ca2+](o) was blocked by calpa in inhibitors (calpeptin and calpain inhibitor-1) indicating a requirement for type II (mM) calpain in the sealing process. Following compression inju ry, the amplitude of the maximal compound action potential conducted throug h the injury site was reduced. The extent of amplitude reduction was increa sed when the tract was superfused with calcium-free Krebs' solution (Ca2+ r eplaced by Mg2+). These results suggest that the fall in [Ca2+](o) seen fol lowing injury in vivo is sufficient to prevent membrane sealing and may par adoxically contribute to axonal dieback, retrograde cell death, and "second ary" axonal disruption.